What is Down Syndrome

Down syndrome is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was identified as a chromosome 21 trisomy by Jérôme Lejeune in 1959.

Down syndrome is a chromosomal condition characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations). The effects and extent of the extra copy vary greatly among people, depending on genetic history, and pure chance.

Often Down syndrome is associated with some impairment of cognitive ability and physical growth, and a particular set of facial characteristics. Individuals with Down syndrome tend to have a lower-than-average cognitive ability, often ranging from mild to moderate disabilities. Many children with Down Syndrome who have received family support, enrichment therapies, and early intervention programme perform better in schools.

Many of the common physical features of Down syndrome may also appear in people with a standard set of chromosomes, including microgenia (an abnormally small chin), an unusually round face, macroglossia (protruding or oversized tongue), an almond shape to the eyes caused by an epicanthic fold of the eyelid, upslanting palpebral fissures (the separation between the upper and lower eyelids), shorter limbs, a single transverse palmar crease (a single instead of a double crease across one or both palms), poor muscle tone, and a larger than normal space between the big and second toes. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions.

Early childhood intervention, screening for common problems, medical treatment where indicated, a conducive family environment, and vocational training can improve the overall development of children with Down syndrome. Education and proper care will improve quality of life significantly, despite genetic limitations.

There are three forms of DS – trisomy 21, translocation and mosaicism.

The most common of the three types of Down Syndrome is often referred to as Trisomy 21. About 95% of people with Down Syndrome have this. This type of Down Syndrome occurs because of an error in cell division. The error happens either before or at the time of conception. What happens is that a pair of the 21st chromosomes in either the egg or the sperm do not separate properly. This extra chromosome is then found in every cell in the body,thereby causing the characteristics of Down Syndrome.

Mosaicism occurs in about 1-2% of all people with Down Syndrome. In this type of Down Syndrome the error in separation of the 21st chromosome occurs in one of the first few cell divisions AFTER fertilization. This causes the fetus to have some cells with 46 chromosomes and some with 47. The cells with 47 chromosomes have one extra 21st chromosome. Because of the fact that not all cells contain the extra chromosome 21 the range of physical problems varies depending on the ratio of cells with 46 chromosomes to those with 47 chromosomes.

Translocation occurs in approximately 3-4% of babies born with Down Syndrome. In this type of Down Syndrome a part of chromosome number 21 breaks off and attaches itself to another chromosome. Often this is chromosome number 14. This causes all cells in the body to have the extra piece of the 21st chromosome. When a child is born with this type of Down Syndrome it could mean that one of the parents is carrying chromosomal material that is unusually arranged.

The test used to determine which type of Down Syndrome is present in an individual is called karyotyping.

Individuals with Down syndrome have a higher risk for many conditions. The medical consequences of the extra genetic material in Down syndrome are highly variable and may affect the function of any organ system or bodily process. Some problems are present at birth, such as certain heart malformations. Others become apparent over time, such as epilepsy.

Congenital heart disease
The incidence of congenital heart disease in children with Down syndrome is up to 50%. A atrioventricular septal defect (AVSD) is the most common form with up to 40% of patients affected. This involves a malfunction of the walls and the valves between the artia and the ventricles. The condition amounts to a hole in the centre of the heart which can gravely affect the direction and pressure of the blood flow and impose a strain on the heart and lungs. Nowadays this can be corrected by major heart surgery in infancy but for a few babies the operation is not medically advisable.

This is closely followed by ventricular septal defect (VSD) that affects approximately 30% of patients. These defects involve an opening in the septum or wall which separates the two ventricles. If a small opening exists, this will not cause strain on the heart and in some cases the opening may close itself. For large defects surgical correction may be necessary again this is usually carried out in the first years of life.

Malignancies
Hematologic malignancies such as leukemia are more common in children with DS. In particular, the risk for acute lymphoblastic leukemia is at least 10 times more common in DS and for the megakaryoblastic form of acute myelogenous leukemia is at least 50 times more common in DS. Transient leukemia is a form of leukemia which is rare in individuals without DS but affects up to 20 percent of newborns with DS. This form of leukemia is typically benign and resolves on its own over several months, though it can lead to other serious illnesses. In contrast to hematologic malignancies, solid tumor malignancies are less common in DS, possibly due to increased numbers of tumor suppressor genes contained in the extra genetic material.

Thyroid disorders
Individuals with DS are at increased risk for dysfunction of the thyroid gland, an organ which helps control metabolism. Low thyroid (hypothyroidism) is most common, occurring in almost a third of those with DS. This can be due to absence of the thyroid at birth (congenital hypothyroidism) or due to attack on the thyroid by the immune system. Reproduction is also affected by DS.

Gastrointestinal
Down syndrome increases the risk of Hirschsprung’s disease, in which the nerve cells that control the function of parts of the colon are not present. This results in severe constipation. Other congenital anomalies occurring more frequently in DS include duodenal atresia, annular pancreas, and imperforate anus. Gastroesophageal reflux disease and celiac disease are also more common among people with DS.

Neurology
Children and adults with DS are at increased risk for developing epilepsy. The risk for Alzheimer’s disease is increased in individuals with DS, with 10-25% of individuals with DS showing signs of AD before age 50, up to 50% with clinical symptoms in the sixth decade, and up to 75% in the 7th decade. This sharp increase in the incidence and prevalence of dementia may be one of the factors driving the decreased life expectancy of persons with Down Syndrome.

Ophthalmology and otolaryngology
Eye disorders are more common in people with DS. Almost half have strabismus, in which the two eyes do not move in tandem. Refractive errors requiring glasses or contacts are also common. Cataracts (opacity of the lens) and glaucoma (increased eye pressures) are also more common in DS. Brushfield spots (small white or grayish/brown spots on the periphery of the iris) may be present.

Other complications
In the past, prior to current treatment, there was a 38-78% incidence of hearing loss in children with Down syndrome. Fortunately, with aggressive, meticulous and compulsive diagnosis and treatment of chronic ear disease (e.g. otitis media, also known as Glue-ear) in children with Down syndrome, approximately 98% of the children have normal hearing levels.

Instability of the atlanto-axial joint occurs in ~15% of people with DS, probably due to ligamental laxity. It may lead to the neurologic symptoms of spinal cord compression. Periodic screening, with cervical x-rays, is recommended to identify this condition.

Other serious illnesses include immune deficiencies.

Children with Down syndrome are often identified at birth as a result of the physical characteristics associated with the syndrome. Some children exhibit only a few characteristics; others exhibit many. Because some of these features are also seen in people without Down syndrome, genetic testing must be done to confirm diagnosis. The most common features associated with Down syndrome include:

Low muscle tone (babies appear “floppy”)

Flat facial features, with a small nose

Upward slant to the eyes

Small skin folds on the inner corner of the eyes

Small, abnormally shaped ears

Single deep crease across the centre of the palm

Hyperflexibility (excessive ability to flex joints)

Fifth finger has only one flexion furrow instead of two

Extra space between the big toe and the second toe

Enlarged tongue that tends to stick out

Children with Down Syndrome have an increased risk to the following medical conditions:

Congenital heart defects

Increased susceptibility to infection

Respiratory problems flu, sinus, bronchitis, pneumonia

Gastrointestinal disorders such as obstructed digestive tract, narrowing of the oesophagus,stomach and intestines and twisting of the bowels

Childhood leukaemia

Ear infection where retention of fluid in the inner ear is a very common cause of hearing and speech difficulties

Down Syndrome is the leading cause of intellectual disability in the world – it is not related to race, nationality, religion or socio-economic status

Down Syndrome is a chromosomal disorder which usually causes delay in physical, intellectual and language development

The incidence of Down Syndrome is 1 in every 660 live births (Malaysia)

The exact causes of the chromosomal rearrangement and primary prevention of Down Syndrome are currently unknown

While the likelihood of giving birth to a child with Down Syndrome increases with maternal age; nevertheless, 80% of babies with Down Syndrome are born to women under 35 years of age, as women in that age group give birth to more babies overall

There is a wide variation in mental abilities, behaviour and physical development in individuals with Down Syndrome. Each individual has his/her own unique personality, capabilities and talents

30%-50% of individuals with Down Syndrome have heart defects and 8-12% have gastrointestinal tract abnormalities present at birth. Most of these defects are correctable by surgery

Individuals with Down Syndrome benefit from loving homes, early intervention, special education, appropriate medical care and positive public attitudes

In adulthood, many persons with Down Syndrome in the US hold jobs, live independently and enjoy recreational opportunities in their communities.